Mary V. Gamble, Ph.D.
Assistant Professor, Environmental Health Sciences

Dr. Gamble's research focuses on nutritional biochemistry at both basic and applied levels. Her earlier work on retinoid metabolism included studies on proteins involved in retinoid transport and in the generation of transcriptionally active retinoic acid metabolites. Her work in international research began with studies on vitamin A deficiency in the Republic of the Marshall Islands and in NE Brazil. Presently, her research is primarily focused on nutrient/environment interactions.

Nutritional Influences on Arsenic Toxicity. The largest known mass exposure to arsenic is presently occurring due to ground water contamination of well water throughout the Ganges-Brahmaputra Delta. There is a significant inter-individual variability in susceptibility to progression from arsenic exposure to clinical manifestations of arsenic toxicity (e.g. skin, lung, liver and bladder cancers). A major project in this lab address the question: What is the impact of nutritional status on As metabolism and toxicity?

Methylation of inorganic arsenic (InAs) is generally considered to be a detoxification pathway. InAs and DNA are both methylated via one-carbon metabolism, a biochemical pathway which is dependent on folate for de novo generation of one-carbon groups, and also uses vitamins B12 and B6 as cofactors. We have therefore set out to determine if nutritional regulation of one-carbon metabolism, specifically folate availability, contributes substantially to the large inter-individual variability observed in InAs and DNA methylation, and thus progression from arsenic exposure to toxicity.

Methylation of InAs also requires that the pentavalent arsenic species first be reduced to trivalent species in a glutathione-dependent process. Regeneration of oxidized glutathione is accomplished by glutathione reductase, an enzyme that is strongly inhibited by arsenic. Another study in the lab explores the relationship between arsenic exposure, antioxidant status, and oxidative DNA damage.

Publications:

Gamble MV, Ahsan H, Liu X, Factor-Litvak P, Ilievski V, Slavkovich V, Parvez F, Graziano JH. Folate and cobalamin deficiencies and hyperhomocysteinemia in Bangladesh. Amer J Clin Nutr 2005;81:1372-1377.

Gamble MV, Liu X, Ahsan H, Pilsner JR, Ilievski V, Slavkovich V, Parvez F, Levy D, Factor-Litvak P, Graziano JH. Folate, homocysteine and arsenic metabolism in arsenic-exposed individuals in Bangladesh. Environ Health Perspect 2005;113:1683-1688.

GambleMV, Palafox NA, Dancheck B, Ricks MO, Briand K, Semba RD. Relationship of vitamin A deficiency, iron deficiency, and inflammation to anemia among preschool children in the Republic of the Marshall Islands, Eur J Clin Nutr 2004;58(10):1396-1401.

Gamble MV, Ramakrishnan R, Palafox NA, Briand K, Berglund L, Blaner WS. Retinol binding protein as a surrogate measure for serum retinol: Studies in vitamin A-deficient children from the Republic of the Marshall Islands. Am J Clin Nutr 73:594-601, 2001.

Semba RD, Yuniar Y, Gamble MV, Natadisastra G, and Muhilal. Assessment of vitamin A status of preschool children in Indonesia using plasma retinol-binding protein. J Trop Pediatr vol. 47, February 2001.

Gamble MV, Mata NL, Tsin A, Mertz JR and Blaner WS. Substrate specificities and 13-cis-retinoic acid inhibition of human, mouse and bovine cis-retinol dehydrogenases. Biochem Biophys Acta 1476(1):3-8, 2000.

Filteau SM, Willumsen JF, Sullivan K, Simmank K, and Gamble M. Use of the retinol-binding protein/transthyretin ratio for assessment of vitamin A status during the acute phase response. Br J Nutr 83(5):513-520, 2000.

Gamble MV, Shang E, Piantedosi Zott R, Mertz JR, Wogelmuth DJ, Blaner WS. Biochemical properties, tissue expression and gene structure of a short chain dehydrogenase/reductase able to catalyze cis-retinol oxidation. J Lipid Res 40:2270-2292, 1999.

Gamble MV and Blaner WS. Factors which affect blood levels of vitamin A. Molecular & Cell Biology Updates. Ed: Livrea MA. Molecular & Cell Biology Updates, Birkhäuser Verlog, Basel, 1-16, 1999.

Vogel S, Gamble MV, Blaner WS. Biosynthesis, absorption, metabolism and transport of retinoids. Ed. Nau H and Blaner WS. In: Handbook of Experimental Pharmacology, vol. 139, Retinoids. Springer Verlag, Heidelberg, 31-95, 1999.